FGF21, the Fountain of Youth

January 18, 2016

FGF21 – The Holy Grail of Longevity 

 Reference: Youm PNAS 2016, Diabetes, Daily Mail

 We’ve found it!   Ponce de Leon had it wrong. It wasn’t in Florida. They found it at Yale. That’s Connecticut.   Published this last week is another article on FGF21. And it shows how you can add 40 % to the longevity of a mouse.   Well, yes, a mouse. Not a human, but we have much the same physiology and just need to find the equivalent in humans.   It’s there. Humans have FGF21 too. 

What is it? Fibroblast Growth Factor 21 is a protein that is produced by the liver in response to a fasting or a ketogenic state.   It does two things that have been known to be linked, but without a clear understanding why. Fasting has been shown to induce longevity by as much as 40% in every mammal ever studied.   And fasting induces your liver to make FGF21.   Fasting also lowers your glucose level, which results in lowering your insulin level. That seems to open the door to the production of FGF21.  

 That means FGF21 might be the mechanism by which you lose weight too. When you cut calories from carb rich sources, you lower your insulin.   That lowers your sugar levels. And that raises FGF21. But just how does FGF21 induce longevity? FGF21 comes from your liver. One of the key problems of aging is that our thymus gland gradually stops training T cells to kill off cancers and viruses.   It’s T cells that are out there all over your body checking out cells that don’t quite look right. T cells kill them off and keep you from getting cancer. We want healthy T cell populations. But with aging, you just don’t have them. If you want them, you have to find a way to make more FGF21.   And that’s just what fasting does. FGF21 is also induced by ketones. That means a state of ketogenesis will increase it. And ketogenesis works when you are eating a diet of fat and very modest protein, but less than 20 grams of carbs a day. And that will explain why the ketogenic diet works in cancer patients. It turns off insulin, a potent growth factor for cancer, and turns on the production of more FGF21. 

Voila! We thought the ketogenic diet was good for helping weight loss, avoiding Alzheimer’s and improving heart disease risk, but now we can unequivocally add cancer avoidance to the list of reasons to eat a higher fat diet. There are other FGF proteins which have their own effects.   FGF23 regulates phosphate excretion. FGF15/19 are two similar ones that help regulate glucose metabolism and bile acid excretion. Go figure. And they are secreted in the terminal ileum. (End of your small bowel). And if you want to go down the rabbit hole of physiology, you might enjoy discovering Klotho proteins that help the FGF hormones bind. And how heparin receptors play a part in the nuanced dance of endocrine hormones. 

 www. What Will Work for Me. This is fascinating to me. We have found the protein hormone that boosts your own immunity. And it works with the same tool we use to fight obesity, heart disease, Alzheimer’s. It’s the human diet.   Now, the new food guidelines came out last week. They made a very timid first step to getting away from carbs and back to fat. They said to cut down on sugar and processed carbs. Finally, a tiny move in the right direction. When they say “load up on butter”, I’ll be proud. Grass raised, by the way. Farmer’s Market is on this winter at the Domes here in Milwaukee. I found some there last week.   

 Pop Quiz

  1. Ponce de Leon believed there was a fountain of youth in Florida.   All we find in Florida is old people still looking for it.   Where is the fountain?
Inside you. Induced by fasting and a ketogenic diet. FGF21 is its name
  1. Ketones will induce the release of FGF21. What are ketones?
The short pieces of chopped up fat molecules that you burn for energy.
  1. Cancers are slowed down with a ketogenic diet? How?
Probably in part by inducing FGF21 which turns on killer T cells – that kill cancer. In part by turning off insulin, that turns on cancer growth. And lowering glucose, that cancer needs to feast on.
  1. FGF21 is made in the liver, but it’s antiaging effect is most pronounced where?
In your beat up old, senescent thymus gland that isn’t making any T cells anymore.
  1. Humans have been shown to live 40% longer, just like other animals. T or F
Not quite yet. The proof isn’t there quite yet, but as many as 100,000 Americans are living on calorie reduced diets specifically because they believe it. FGF21 may be the key. Stay tuned!